A cell atlas of mouse lung development reveals a signaling role for lung basophils in alveolar macrophage maturation

Lung development and function arises from the interactions between diverse cell types and lineages. Using single cell RNA-seq we characterize the cellular composition of the lung during development and identify vast dynamics in both the composition of cells and their molecular characteristics. Analyzing 818 ligand-receptor interaction pairs within and between cell lineages, we identify broadly interacting cells, including AT2, ILC and basophils. Using IL33-receptor knockout mice and in vitro experiments, we show that basophils establish a lung-specific function imprinted by IL-33 and GM-CSF, characterized by unique signaling of cytokines and growth factors important for stromal, epithelial and myeloid cell fates. Antibody depletion strategies, diphtheria toxin–mediated selective depletion of basophils, and co-culture studies, show that lung resident basophils are important regulators of alveolar macrophage development and function. Together, our study demonstrates how whole tissue cell interaction analysis on the single cell level can broaden our understanding of cellular networks in health and disease. Overall design: Transcriptional profiling of single cells from the different timepoints of lung development, generated from deep sequencing of tens of thousands of cells, sequenced in several batches on illumina Nextseq500 metadata.txt: Meta data file associating each single cell with its amplification batch and index sorting readouts

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Cohen M, Giladi A, Gorki AD, Solodkin DG, Zada M, Hladik A, Miklosi A, Salame TM, Halpern KB, David E, Itzkovitz S, Harkany T, Knapp S, Amit I